Inhibition of CaMKII phosphorylation of RyR2 prevents induction of atrial fibrillation in FKBP12.6 knockout mice.

Abstract

FKBP12.6 mice exhibit AF caused by SR Ca(2+) leak, Na(+)/Ca(2+)-exchanger activation, and DADs, which promote triggered activity.

Genetic inhibition of RyR2-S2814 phosphorylation prevents AF induction in FKBP12.6-/- mice by suppressing SR Ca(2+) leak and DADs. These results suggest suppression of RyR2-S2814 phosphorylation as a potential anti-AF therapeutic target.

Full Text

• DOI - Circulation research (DOI)
• Swets Information Services - full-text online
• Ovid Technologies, Inc. - full-text online
• Lippincott Williams & Wilkins - full-text online
• HighWire Press - full-text online

Subjects

• Animals
• Atrial Fibrillation
• Calcium
• Calcium-Binding Proteins
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Heart Atria
• Mice
• Mice, Knockout
• Models, Animal
• Myocytes, Cardiac
• Patch-Clamp Techniques
• Phosphorylation
• Protein Subunits
• Ryanodine Receptor Calcium Release Channel
• Sarcoplasmic Reticulum
• Tacrolimus Binding Proteins

Similar articles

• Inhibition of CaMKII phosphorylation of RyR2 prevents inducible ventricular arrhythmias in mice with Duchenne muscular dystrophy. (2012-12-12)
• Calcium leak through ryanodine receptors leads to atrial fibrillation in 3 mouse models of catecholaminergic polymorphic ventricular tachycardia. (2012-07-24)
• Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model. (2013-04-23)
• Arrhythmogenesis in catecholaminergic polymorphic ventricular tachycardia: insights from a RyR2 R4496C knock-in mouse model. (2006-08-04)
• Conditional FKBP12.6 overexpression in mouse cardiac myocytes prevents triggered ventricular tachycardia through specific alterations in excitation-contraction coupling. (2008-04-08)
• Ca2+/calmodulin-dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2+ leak in heart failure. (2005-12-12)
• CaMKII-dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels in right atrial myocardium of patients with atrial fibrillation. (2010-04-02)
• Epac2 mediates cardiac β1-adrenergic-dependent sarcoplasmic reticulum Ca2+ leak and arrhythmia. (2013-01-30)
• In cardiomyocytes, binding of unzipping peptide activates ryanodine receptor 2 and reciprocally inhibits calmodulin binding. (2012-12-11)

Authors

• Na Li
• Tiannan Wang
• Wei Wang
• Michael J Cutler
• Qiongling Wang
• Niels Voigt
• David S Rosenbaum
• Dobromir Dobrev
• Xander H T Wehrens

Publication date

2012-02-03

Journal

Journal topics

• Cardiovascular System

Language

Eng.

Copyright

Circulation research

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.

Release reference

Circ Res. 2012 Feb;110(3):465-70

Related books

• Books of Animals
• Books of Atrial Fibrillation
• Books of Calcium
• Books of Calcium-Binding Proteins
• Books of Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Books of Cardiovascular System
• Books of Heart Atria
• Books of Mice
• Books of Mice, Knockout
• Books of Models, Animal
• Books of Myocytes, Cardiac
• Books of Patch-Clamp Techniques
• Books of Phosphorylation
• Books of Protein Subunits
• Books of Ryanodine Receptor Calcium Release Channel
• Books of Sarcoplasmic Reticulum
• Books of Tacrolimus Binding Proteins